Systematic studies of host defenses against human T cell leukemia/lymphoma viruses (HTLV) I and II have been made possible by the recent identification of the viruses, their association with leukemia/lymphoma, and the development of methods for assay of infectivity and transformation. Effective control of many viral infections has come through understanding and application of the body's defense mechanisms. Thus the conditions are available for a systematic study of the various defenses during HTLV infection and transformation. The specific aims are to determine: (1) the relative effectiveness of the known host defenses (antibody, cell mediated immunity and interferon) against HTLV I and II infectivity and multiplication, and against transformed cells; (2) whether transformed cells from patients are resistant to the host defenses; (3) the role of the newly described natural body inhibitors of viruses (CVI and amines); and (4) whether the findings can be used to help design intervention studies in animal models and patients. The experimental approach will be to determine the effects and mechanisms of action of the various host defenses against: (1) HTLV infectivity (virus pseudotype plaque reduction, reverse transcriptase yield, and syncytium formation), (2) transformation of cells, and (3) mulitiplication and survival of transformed cells from patients and from in vitro transformed cells. Some specific questions to be addressed include: are ADCC effector cells from patients ineffective, as reported and why are they ineffective?; will the most active antiviral and cytolytic mechanisms of interferon also suppress HTLV infection and transformation?; will the newly recognized host defenses (CVI and amines) be as effective against HTLV as they are against other viruses including animal retroviruses?; and will combinations of defenses suppress transforming infections or "eradicate" tumor cells, as found in other systems?